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A PINCH-1-Smurf1 signaling axis mediates mechano-regulation of BMPR2 and stem cell differentiation.
- Source :
-
The Journal of cell biology [J Cell Biol] 2019 Nov 04; Vol. 218 (11), pp. 3773-3794. Date of Electronic Publication: 2019 Oct 02. - Publication Year :
- 2019
-
Abstract
- Mechano-environment plays multiple critical roles in the control of mesenchymal stem cell (MSC) fate decision, but the underlying signaling mechanisms remain undefined. We report here a signaling axis consisting of PINCH-1, SMAD specific E3 ubiquitin protein ligase 1 (Smurf1), and bone morphogenetic protein type 2 receptor (BMPR2) that links mechano-environment to MSC fate decision. PINCH-1 interacts with Smurf1, which inhibits the latter from interacting with BMPR2 and consequently suppresses BMPR2 degradation, resulting in augmented BMP signaling and MSC osteogenic differentiation (OD). Extracellular matrix (ECM) stiffening increases PINCH-1 level and consequently activates this signaling axis. Depletion of PINCH-1 blocks stiff ECM-induced BMP signaling and OD, whereas overexpression of PINCH-1 overrides signals from soft ECM and promotes OD. Finally, perturbation of either Smurf1 or BMPR2 expression is sufficient to block the effects of PINCH-1 on BMP signaling and MSC fate decision. Our findings delineate a key signaling mechanism through which mechano-environment controls BMPR2 level and MSC fate decision.<br /> (© 2019 Guo et al.)
- Subjects :
- Cells, Cultured
Humans
Membrane Proteins metabolism
Signal Transduction
Adaptor Proteins, Signal Transducing metabolism
Bone Morphogenetic Protein Receptors, Type II metabolism
Cell Differentiation
LIM Domain Proteins metabolism
Stem Cells cytology
Stem Cells metabolism
Ubiquitin-Protein Ligases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-8140
- Volume :
- 218
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 31578224
- Full Text :
- https://doi.org/10.1083/jcb.201902022